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Rat Sertoli cell aromatase cytochrome P450: regulation by cell culture conditions and relationship to the state of cell differentiation.

Primary cultures of immature rat Sertoli cells in plastic dishes are highly responsive to follicle stimulating hormone (FSH) and its second messenger, cAMP, in metabolizing testosterone to estradiol, thus indicating the presence of an active, hormone-regulated aromatase cytochrome P450 (P450arom). However, in vivo studies indicated that P450arom is FSH-responsive only in very young animals, where the cells have not yet differentiated, but they lose this ability later on in development. Sertoli cells grown on Matrigel (a reconstituted basement membrane), laminin (a basement membrane component), or in bicameral chambers coated with Matrigel, assume structural and functional characteristics more similar to that of in vivo differentiated Sertoli cells. When the cells were cultured on laminin or Matrigel, the FSH- and cAMP-induced estradiol production was greatly reduced by 30 and 60%, respectively. When Sertoli cells were cultured in bicameral chambers coated with Matrigel, no induction of testosterone aromatization by FSH or cAMP was observed. However, FSH-induced cAMP formation was greater when the cells were cultured on basement membrane or in the chambers than on plastic dishes. These results suggest that culture conditions favoring the assumption by Sertoli cells of a phenotype closer that of the differentiated cells in vivo (tall columnar and highly polarized) suppress the induction of P450arom by FSH and cAMP. We then examined the mechanism(s) by which cell phenotype affects p450arom activity. Northern blot analyses of Sertoli cell RNA revealed one major band of 1.9 Kb and two minor bands of 3.3 and 5.2 Kb. However, there were no changes at the level of the expression of P450arom messenger RNA under the different culture conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[On the problem og higher fungi origin: Florideae hypothesis].

The history and current state of the hypothesis of the origin of higher fungi (Ascomycetes and Basidiomycetes) and red algae from the common ancestor (Florideae) were analysed. Initially the hypothesis was based on similarity of their vegetative and generative structures (Sachs, 1874; Dodge, 1914; Chadefaund, 1953, 1972, etc.), but later it was confirmed by ultrastructural data (Demoulin, 1974; Kohlmeyer, 1975). It appears to be very useful for the study of the development of terrestrial flora (Church, 1921; Kohlemeyer, Kohlmeyer, 1979; Atsatt, 1988) and regularities in morphological evolution of higher fungi (Corner, 1964, 1970; Chadefaud, 1960, 1982, 1984). Description of the order Spathulosporales (Kohlmeyer, 1973), combining the characters of Ascomycetes and parasitic Florideae, was one of the most important fact leading to the wide recognition of the hypothesis in 1970-80s (Cavalier-Smith, 1978; Taylor, 1978; Dodge, 1980; Hawksworth, 1982; Goff, 1983; Coff, Coleman, 1985). Today, however, Florideae hypothesis is not confirmed by molecular data and replaced by alternative hypothesis of Eumycota origin. Summarizing data on molecular systematic of fungi, one could affirm with confidence: 1). Chitincontaining fungi are closer to multicellular animals and green plants than to Rhodophyta; 2). Rhodophyta and Chlorophyta are monophyletic group; 3). There is no single-valued molecular data on taxonomic distance between higher fungi, Chytridiomycetes; Rhodophyta, Chlorophyta and Metazoa. Thus, the current data could not testify against Florideae hypothesis. It is possible to adjust them with the idea of B.M. Kozo-Polyansky (1927) about existence of "Chloroflorodeae" group that is original for terrestrial flora; the hypothesis about closeness of Chlorophyta and Rhodophyta, as well as Chlorophyta and Eumycota, does not contradict molecular data (Stiller, Hall, 1997). The author believes that we need molecular study of the whole "stem" of chlorobionta, especially groups that are close to its basis. It will will help to understand the relationships between Rhodophyta, giant conglomeration of "green algae", chitin-containing fungi, Prasinophyceae and different groups of zoomastigot with maximal resolution--the level of orders or groups of orders. Only such investigation could provide the material for molecular support of phylogenetic constructions. Up to moment Florideae hypothesis is able to exist together with the other ideas.

Ascomycota↗

The wounded male persona and the mysterious feminine in the poetry of James Wright: a study in the transformation of the self.

James Wright's work is multilayered. Taken as a whole, which Annie Wright's beautiful compilation, Above the River, allows one to do, Wright's poems (as well as his masterful "prose poems") have a pattern akin to a mythic cycle. "Mythemes" (Lévi-Strauss, 1979) recur as dialectic opposites from one poem to another, whether the abandoned male and mysterious woman, humankind and nature, blindness and seeing, secrets and revelation. Suggestive and symbolic forms such as birds, horses, earth, sky, the destitute, rivers, and adolescence weave themselves throughout in inner and outer "landscapes" of images and experiential moments. There is a frequent shift of "gestalts" between the inner world and external reality. Such a "blooming, buzzing confusion" of internal and external referents might appear to be psychotic and imply a loss of "reality testing." Chassaguet-Smirgel (1988), citing Oscar Wilde's The Picture of Dorian Gray as an example, contended that the artist narrowly averts psychosis by transforming it into a work of art. Surrealists, for whom the psychoanalyst Jacques Lacan was an important figure (cf. Sarup, 1992, pp. 17-27), elevated psychosis to the status of art, and Wright has been considered to be a surrealistic poet, although he himself denied such an affiliation. Hall (Wright, 1990, Introduction, pp. xxiii-xxxvii) suggests that Wright, in addition to an extensive history of alcoholism, from which he seemed to recover towards the end of his life, suffered from a major mental illness, which included episodes of severe depression, hospitalizations, and at least one suicide attempt. The severity of the asceticism and the extreme damage to the self in some Wright's work suggests their roots in early traumatic experiences. (A terribly damaged yet heroic personage, whose disfigurement perhaps symbolizes the poet's trauma, is "Hook" [ATR, pp. 315-316], about a man who gives his last few cents to the poet with a hook replacing his amputated hand.) Not enough is known about Wright's childhood to attempt to reconstruct such a trauma, and a definitive biography is long overdue. (Wright died in 1980). However, the concept of "soul murder" as used by Shengold (1989) with respect to psychological trauma does seem pertinent. For example, Wright's powerful identification with the downtrodden, and especially with certain murderers (Doty, Judas) echoes the paranoiac Schreber's identification with his abusive father as "soul murderer": "I, myself, have been 'represented' as the one who had committed soul murder" (Shengold, 1989, p. 22, quoting Schreber). Certainly, the theme of damage to the self is prominent in Wright, and the poet's striving for reparation, restitution, and the restoration of lost goodness is not only characteristic of Melanie Klein's "depressive position" (Segal, 1980, pp. 76-89), which she saw as a normal developmental process, but also of the character structures of profoundly traumatized individuals. In addition, the rapid, "leaping" shifts of imagery in Wright's poems bear some resemblance to the shifts in mood and the dissociated and "autohypnotic" states (Shengold, 1989, pp. 138-154) of posttraumatic stress and related disorders. However much that may be the case, Wright's work moves toward healing and integration, and forces us to reconsider the psychoanalytic shibboleth that all that represents a lack of distinctiveness between self and other is pathological. This assumption denies the richness of that part of the psyche which originates in the symbiotic union of mother and infant. Wright's work does not so much force us to doubt our own perceptions of reality as it gently yet forthrightly guides us into other realms where feeling and thought are in dialogue, where the uniquely human and the universal mythos converge, and where--perhaps most importantly--possibility and transformation are imminent. The abandoned male persona and the mysterious feminine are part of that world, that cosmos, that Wright has cr

Female↗

Toxic effects of nonsteroidal anti-inflammatory drugs in overdose. An overview of recent evidence on clinical effects and dose-response relationships.

Nonsalicylate, nonsteroidal anti-inflammatory drugs (NSAIDs) can be divided into 4 chemical classes: acetic acids, fenamic acids, oxicams and propionic acids. Most NSAID overdoses result in a benign outcome. Of 50,614 exposures reported to poison centres in the United States in a 2-year period, 131 (0.26%) had a major outcome, with 10 deaths. Despite the generally mild effects reported in large patient series, isolated case reports have documented serious toxicity, such as seizures, hypotension, apnoea, coma and renal failure. The majority of these consequences occur after ingestion of substantial quantities by adults attempting suicide. Rarely, with ibuprofen and piroxicam, children who ingest small amounts in accidental exposure develop serious toxicity. Typical signs and symptoms of NSAID overdose include nausea, vomiting, headache, drowsiness, blurred vision and dizziness. Seizures are rarely documented across all NSAID classes, with the exception of mefenamic acid (where seizures occur in over one-third of cases), or following massive ingestion of other agents. Drugs in the propionic acid group have produced metabolic acidosis, respiratory depression and coma in severe cases. Ibuprofen is the agent with the most published data on overdose, probably because it is available without a prescription in many countries. Symptoms are unlikely after ingestion of 100 mg/kg or less, and are usually not life-threatening unless more than 400 mg/kg is ingested. There is some relationship between plasma concentrations and the potential for development of symptoms, but plasma concentrations have no impact on treatment decisions. Treatment of NSAID overdose is entirely supportive. Recent trends in emergency department procedures regarding gastric decontamination are evolving towards the recommended administration of activated charcoal without gastric emptying in patients presenting more than 1 hour after ingestion, although gastric lavage, followed by administration of activated charcoal, may be advisable in patients who present earlier. Home administration of syrup of ipecac is still recommended if treatment is given shortly after ingestion, with a few exceptions: for example, ipecac is contraindicated after ingestion of mefenamic acid or ibuprofen in amounts greater than 400 mg/kg. Urine alkalinisation and diuresis have been recommended to enhance the elimination of NSAIDs, based on a pKa in the range of 3 to 5. However, because the drugs are universally highly protein bound, with little unchanged renal excretion, this technique is not likely to be beneficial. Haemodialysis is also unlikely to enhance elimination, but may be required if oliguric renal failure develops. Multiple dose activated charcoal may be useful in enhancing elimination of NSAIDs with long half-lives, such as piroxicam and sulindac.

Anti-Inflammatory Agents, Non-Steroidal↗